2-{[1-(4-{[3-({3-[(NODAGA-Ttds)-methyl-amino]-propyl}-methyl-amino)-propyl]-methyl-carbamoyl}-2-isopropyl-phenyl)-5-(2,6-dimethoxy-phenyl)-1H-pyrazole-3-carbonyl]-amino}-adamantane-2-carboxylic acid | 1613332-67-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-{[1-(4-{[3-({3-[(NODAGA-Ttds)-methyl-amino]-propyl}-methyl-amino)-propyl]-methyl-carbamoyl}-2-isopropyl-phenyl)-5-(2,6-dimethoxy-phenyl)-1H-pyrazole-3-carbonyl]-amino}-adamantane-2-carboxylic acid
• 英文别名: US10799605, Example 12；2-[[1-[4-[3-[3-[[4-[3-[2-[2-[3-[[4-[4,7-bis(carboxymethyl)-1,4,7-triazonan-1-yl]-4-carboxybutanoyl]amino]propoxy]ethoxy]ethoxy]propylamino]-4-oxobutanoyl]-methylamino]propyl-methylamino]propyl-methylcarbamoyl]-2-propan-2-ylphenyl]-5-(2,6-dimethoxyphenyl)pyrazole-3-carbonyl]amino]adamantane-2-carboxylic acid
• CAS: 1613332-67-4
• 化学式: C₇₁H₁₀₇N₁₁O₁₈
• 分子量: 1402.69
• InChiKey: JBWZSQAATPMTHP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.6
• 重原子数：
  100
• 可旋转键数：
  43
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  354
• 氢给体数：
  7
• 氢受体数：
  23

反应信息

• 作为产物：
  描述：

  2-({5-(2,6-dimethoxy-phenyl)-1-[2-isopropyl-4-(methyl-{3-[methyl-(3-methylamino-propyl)-amino]-propyl}-carbamoyl)-phenyl]-1H-pyrazole-3-carbonyl}-amino)-adamantane-2-carboxylic acid tert-butyl ester trityl resin 、 2-(4,7-bis-tert-butoxycarbonylmethyl-[1,4,7]triazonan-1-yl)-4-[3-(2-{2-[3-(3-carboxy-propionylamino)-propoxy]-ethoxy}-ethoxy)-propylcarbamoyl]-butyric acid tert-butyl ester 在 N-羟基-7-氮杂苯并三氮唑 、 N,N-二异丙基乙胺 、 N,N'-二异丙基碳二亚胺 、 三异丙基硅烷 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 、 水 为溶剂， 以48.8%的产率得到2-{[1-(4-{[3-({3-[(NODAGA-Ttds)-methyl-amino]-propyl}-methyl-amino)-propyl]-methyl-carbamoyl}-2-isopropyl-phenyl)-5-(2,6-dimethoxy-phenyl)-1H-pyrazole-3-carbonyl]-amino}-adamantane-2-carboxylic acid
  参考文献：
  名称：

  [EN] NEUROTENSIN RECEPTOR LIGANDS
  [FR] LIGANDS DES RÉCEPTEURS DE LA NEUROTENSINE

  摘要：

  公开号：

  WO2014086499A8

文献信息

• Conjugate comprising a neurotensin receptor ligand and use thereof
  申请人：3B PHARMACEUTICALS GMBH

  公开号：US10799605B2

  公开（公告）日：2020-10-13

  The present invention is related to a conjugate comprising a structure of general formula (1) [TM1]-[AD1]-[LM]-[AD2]-[TM2] (1), wherein TM1 is a first targeting moiety, wherein the first targeting moiety is capable of binding to a first target, AD1 is a first adapter moiety or is absent, LM is a linker moiety or is absent, AD2 is a second adapter moiety or is absent, and TM2 is a second targeting moiety, wherein the second targeting moiety is capable of binding to a second target; wherein the first targeting moiety and/or the second targeting moiety is a compound of formula (2): wherein R1 is selected from the group consisting of hydrogen, methyl and cyclopropylmethyl; AA-COOH is an amino acid selected from the group consisting of 2-amino-2 adamantane carboxylic acid, cyclohexylglycine and 9-amino-bicyclo[3.3.1]nonane-9 carboxylic acid; R2 is selected from the group consisting of (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3C8)cycloalkylmethyl, halogen, nitro and trifluoromethyl; ALK′ is (C2-C5)alkylidene; R3, R4 and R5 are each and independently selected from the group consisting of hydrogen and (C1-C4)alkyl under the proviso that one of R3, R4 and R5 is of the following formula (3) wherein ALK′ is (C2-C5)alkylidene; R6 is selected from the group consisting of hydrogen and (C1-C4)alkyl; and R7 is a bond; or a pharmacologically acceptable salt, solvate or hydrate thereof.

  本发明涉及一种包含通式（1）[TM1]-[AD1]-[LM]-[AD2]-[TM2]（1）结构的共轭物，其中 TM1 是第一靶向分子，其中第一靶向分子能够与第一靶点结合、AD1 是第一适配基团或不存在，LM 是连接基团或不存在，AD2 是第二适配基团或不存在，TM2 是第二靶向基团，其中第二靶向基团能够与第二靶点结合；其中第一靶向分子和/或第二靶向分子是式 (2) 的化合物：其中 R1 选自由氢、甲基和环丙基甲基组成的组； AA-COOH 是选自由 2-氨基-2-金刚烷羧酸、环己基甘氨酸和 9-氨基-双环[3.3.R2选自由(C1-C6)烷基、(C3-C8)环烷基、(C3C8)环烷基甲基、卤素、硝基和三氟甲基组成的组；ALK′为(C2-C5)亚烷基；R3、R4 和 R5 各自独立地选自氢和(C1-C4)烷基组成的组，但 R3、R4 和 R5 中的一个应符合下式(3)，其中 ALK′为(C2-C5)亚烷基；R6 选自氢和(C1-C4)烷基组成的组；R7 为键；或其药理学上可接受的盐、溶液或水合物。
• Neurotensin receptor ligands
  申请人：3B Pharmaceuticals GmbH

  公开号：US10961199B2

  公开（公告）日：2021-03-30

  The present invention is related to a compound of formula (I) wherein R1 is selected from the group consisting of hydrogen, methyl and cyclopropylmethyl; AA-COOH is an amino acid selected from the group consisting of 2-amino-2-adamantane carboxylic acid, cyclohexylglycine and 9-amino-bicyclo[3.3.1]nonane-9-carboxylic acid; R2 is selected from the group consisting of (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3-C5)cycloalkylmethyl, halogen, nitro and trifluoromethyl; ALK is (C2-C5)alkylidene; R3, R4 and R5 are each and independently selected from the group consisting of hydrogen and (C1-C4)alkyl under the proviso that one of R3, R4 and R5 is of the formula (II) wherein ALK′ is (C2-C5)alkylidene; R6 is selected from the group consisting of hydrogen and (C1-C4)alkyl; and R7 is selected from the group consisting of H and an Effector moiety; or a pharmacologically acceptable salt, solvate or hydrate thereof.

  本发明涉及式(I)化合物 其中 R1 选自氢、甲基和环丙基甲基组成的组；AA-COOH 是选自 2-氨基-2-金刚烷羧酸、环己基甘氨酸和 9-氨基-双环[3.3.1]壬烷-9-羧酸组成的组的氨基酸；R2 选自(C1-C6)烷基、(C3-C8)环烷基、(C3-C5)环烷基组成的组。R2选自由(C1-C6)烷基、(C3-C8)环烷基、(C3-C5)环烷基甲基、卤素、硝基和三氟甲基组成的组；ALK为(C2-C5)亚烷基；R3、R4和R5各自独立地选自由氢和(C1-C4)烷基组成的组，但R3、R4和R5中的一个为式(II)，其中ALK′为(C2-C5)亚烷基；R6 选自由氢和（C1-C4）烷基组成的组；以及 R7 选自由 H 和效应分子组成的组；或其药理学上可接受的盐、溶液或水合物。
• NEUROTENSIN RECEPTOR LIGANDS
  申请人：3B Pharmaceuticals GmbH

  公开号：EP2928870B1

  公开（公告）日：2020-04-08
• CONJUGATE COMPRISING A NEUROTENSIN RECEPTOR LIGAND AND USE THEREOF
  申请人：3B PHARMACEUTICALS GMBH

  公开号：US20170119913A1

  公开（公告）日：2017-05-04

  The present invention is related to a conjugate comprising a structure of general formula (1) [TM1]-[AD1]-[LM]-[AD2]-[TM2] (1), wherein TM1 is a first targeting moiety, wherein the first targeting moiety is capable of binding to a first target, AD1 is a first adapter moiety or is absent, LM is a linker moiety or is absent, AD2 is a second adapter moiety or is absent, and TM2 is a second targeting moiety, wherein the second targeting moiety is capable of binding to a second target; wherein the first targeting moiety and/or the second targeting moiety is a compound of formula (2): wherein R 1 is selected from the group consisting of hydrogen, methyl and cyclopropylmethyl; AA-COOH is an amino acid selected from the group consisting of 2-amino-2 adamantane carboxylic acid, cyclohexylglycine and 9-amino-bicyclo[3.3.1]nonane-9 carboxylic acid; R 2 is selected from the group consisting of (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 C 8 )cycloalkylmethyl, halogen, nitro and trifluoromethyl; ALK′ is (C 2 -C 5 )alkylidene; R 3 , R 4 and R 5 are each and independently selected from the group consisting of hydrogen and (C 1 -C 4 )alkyl under the proviso that one of R 3 , R 4 and R 5 is of the following formula (3) wherein ALK′ is (C 2 -C 5 )alkylidene; R 6 is selected from the (2) group consisting of hydrogen and (C 1 -C 4 )alkyl; and R 7 is a bond; or a pharmacologically acceptable salt, solvate or hydrate thereof.
• [EN] CONJUGATE COMPRISING A NEUROTENSIN RECEPTOR LIGAND AND USE THEREOF<br/>[FR] CONJUGUÉ COMPRENANT UN LIGAND DE RÉCEPTEUR DE NEUROTENSINE ET SON UTILISATION
  申请人：3B PHARMACEUTICALS GMBH

  公开号：WO2015188934A1

  公开（公告）日：2015-12-17

  The present invention is related to a conjugate comprising a structure of general formula (1) [TM1] - [AD1] - [LM] - [AD2] - [TM2] (1), wherein TM1 is a first targeting moiety, wherein the first targeting moiety is capable of binding to a first target, AD1 is a first adapter moiety or is absent, LM is a linker moiety or is absent, AD2 is a second adapter moiety or is absent, and TM2 is a second targeting moiety, wherein the second targeting moiety is capable of binding to a second target; wherein the first targeting moiety and/or the second targeting moiety is a compound of formula (2): wherein R1 is selected from the group consisting of hydrogen, methyl and cyclopropylmethyl; AA-COOH is an amino acid selected from the group consisting of 2-amino-2 adamantane carboxylic acid, cyclohexylglycine and 9-amino-bicyclo[3.3.1]nonane-9 carboxylic acid; R2 is selected from the group consisting of (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3C8)cycloalkylmethyl, halogen, nitro and trifluoromethyl; ALK' is (C2-C5)alkylidene; R3, R4 and R5 are each and independently selected from the group consisting of hydrogen and (C1-C4)alkyl under the proviso that one of R3, R4 and R5 is of the following formula (3) wherein ALK' is (C2-C5)alkylidene; R6 is selected from the group consisting of hydrogen and (C1-C4)alkyl; and R7 is a bond; or a pharmacologically acceptable salt, solvate or hydrate thereof.